Shikonin mitigates ovariectomy-induced bone loss and RANKL-induced osteoclastogenesis via TRAF6-mediated signaling pathways - 19/04/20
, Zijun Yan b, 1 , Yiran Wang c, 1 , Yilin Yang c, 1 , Mengxi Cai b , Chunyou Huang b , Bo Li a , Mingyuan Yang a , Xiaoyi Zhou a , Xianzhao Wei a , Changwei Yang a , Ziqiang Chen a , Xiao Zhai a, ⁎ , Ming Li a, ⁎ Bienvenue sur EM-consulte, la référence des professionnels de santé.
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| pages | 12 |
| Iconographies | 8 |
| Vidéos | 0 |
| Autres | 0 |
Graphical abstract |
Our findings demonstrate that shikonin reduces osteoclastogenesis in vivo and in vitro. The inhibitory effect is induced by suppression of the interaction between RANK and TRAF6 and the downstream MAPK and NF-κB signaling pathways, which suggest that shikonin might be potentially used for the treatment of postmenopausal osteoporosis.
Highlights |
• | Shikonin prevents bone loss by inhibiting osteoclastogenesis in vitro and in ovariectomized mice in vivo. |
• | Shikonin reduces the RANKL-induced activation of the NF-κB and MAPK signaling pathways. |
• | Shikonin mitigates M-CSF-induced RANK expression and the RANKL-induced RANK-TRAF6 association. |
Abstract |
Background |
Postmenopausal osteoporosis results from estrogen withdrawal and is characterized mainly by bone resorption. Shikonin is a bioactive constitute of Chinese traditional herb which plays a role in antimicrobial and antitumor activities. The study was designed to investigate the role of shikonin on postmenopausal osteoporosis and explore its underlying mechanisms.
Methods |
Immunofluorescence staining was performed to evaluate the effects of shikonin on actin ring formation. The expression levels of the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathway were determined by Western blot analysis. To determine whether shikonin influences the receptor activator of nuclear factor-κB ligand (RANKL)-induced association between receptor activator of NF-κB (RANK) and tumor necrosis factor receptor associated factor 6 (TRAF6), immunofluorescence staining and immunoprecipitation experiments were performed. During our validation model, histomorphometric examination and micro-computed tomography (CT) were conducted to assess the morphology of osteoporosis.
Results |
Shikonin prevented bone loss by inhibiting osteoclastogenesis in vitro and improving bone loss in ovariectomized mice in vivo. At the molecular level, Western blot analysis indicated that shikonin inhibited the phosphorylation of inhibitor of NF-κB (IκB), P50, P65, extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), and P38. Interaction of TRAF6 and RANK was prevented, and downstream MAPK and NF-κB signaling pathways were downregulated.
Conclusion |
Osteoclastic bone resorption was reduced in the presence of shikonin in vitro and in vivo. Shikonin is a promising candidate for treatment of postmenopausal osteoporosis.
Le texte complet de cet article est disponible en PDF.Keywords : Osteoporosis, Shikonin, Osteoclastogensis, TRAF6, Osteoclast
Plan
Vol 126
Article 110067- juin 2020 Retour au numéro
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